GOUT DRUGS SQUARE OFF IN TRIAL
May 28, 2022 - Gout affects about 4% of the U.S. population. It is marked by recurrent episodes of painful, swollen joints that develop quickly, peak in 6 - 12 hours, and then slowly resolve over 7 - 10 days. Gout is primarily driven by elevated uric acid levels, and the best treatment is prevention with medications that reduce uric acid accumulation. Four urate-lowering medications are currently available: allopurinol and febuxostat (xanthine oxidase inhibitors), probenecid (uricosuric agent), and pegloticase (recombinant uricase). [Mechanism of urate-lowering drugs illustration] The American College of Rheumatology (ACR) recommends allopurinol be used first and febuxostat second. Febuxostat carries a boxed warning about the possibility of increased cardiovascular death, and the ACR says that it should be avoided in patients with cardiovascular disease. A recent trial compared the two drugs head-to-head.
A study published in NEJM Evidence enrolled 940 adults with gout and uric acid levels ≥ 6.8 mg/dl. Patients were randomized to allopurinol (up to 800 mg/day) or febuxostat (up to 120 mg/day), and the drugs were titrated to achieve a uric acid level of less than 6 mg/dl. After 48 weeks of titration and dose stabilization, patients entered a 23-week observation phase where the number of patient-reported gout attacks was recorded. At the end of the study, 36.5% of allopurinol-treated patients reported one or more gout attacks compared to 43.5% of febuxostat-treated patients (diff -7, 95%CI [-∞ to -1.2]). Reductions in uric acid levels were similar between groups, with 81% of allopurinol-treated patients and 78% of febuxostat-treated patients achieving a level of less than 6 mg/dl. Adverse events were comparable, and surprisingly, the number of cardiovascular events was higher in the allopurinol group. [SH review]
Interesting findings from this study include the following: (1) allopurinol was superior to febuxostat at preventing gout attacks, (2) even though most patients achieved a target uric acid level of less than 6 mg/dl, 35 - 45% still reported gout flares, (3) cardiovascular events were higher in the allopurinol group.
As far as acute flares are concerned, an open-label trial (N=399) published in 2020 found that colchicine and naproxen were equally effective in hastening resolution, which means that most patients can self-treat gout attacks at home with over-the-counter NSAIDs. [SH review]